Search results for: signet ring cell cancer
Commenced in January 2007
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Edition: International
Paper Count: 5369

Search results for: signet ring cell cancer

3059 Assessment and Adaptation Strategy of Climate Change to Water Quality in the Erren River and Its Impact to Health

Authors: Pei-Chih Wu, Hsin-Chih Lai, Yung-Lung Lee, Yun-Yao Chi, Ching-Yi Horng, Hsien-Chang Wang

Abstract:

The impact of climate change to health has always been well documented. Amongst them, water-borne infectious diseases, chronic adverse effects or cancer risks due to chemical contamination in flooding or drought events are especially important in river basin. This study therefore utilizes GIS and different models to integrate demographic, land use, disaster prevention, social-economic factors, and human health assessment in the Erren River basin. Therefore, through the collecting of climatic, demographic, health surveillance, water quality and other water monitoring data, potential risks associated with the Erren River Basin are established and to understand human exposure and vulnerability in response to climate extremes. This study assesses the temporal and spatial patterns of melioidosis (2000-2015) and various cancer incidents in Tainan and Kaohsiung cities. The next step is to analyze the spatial association between diseases incidences, climatic factors, land uses, and other demographic factors by using ArcMap and GeoDa. The study results show that amongst all melioidosis cases in Taiwan, 24% cases (115) residence occurred in the Erren River basin. The relationship between the cases and in Tainan and Kaohsiung cities are associated with population density, aging indicator, and residence in Erren River basin. Risks from flooding due to heavy rainfall and fish farms in spatial lag regression are also related. Through liver cancer, the preliminary analysis in temporal and spatial pattern shows an increases pattern in annual incidence without clusters in Erren River basin. Further analysis of potential cancers connected to heavy metal contamination from water pollution in Erren River is established. The final step is to develop an assessment tool for human exposure from water contamination and vulnerability in response to climate extremes for the second year.

Keywords: climate change, health impact, health adaptation, Erren River Basin

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3058 Identification of Potential Small Molecule Inhibitors Against β-hCG for Cancer Therapy: An In-Silico Study

Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

Abstract:

hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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3057 The Proton Flow Battery for Storing Renewable Energy: A Theoretical Model of Electrochemical Hydrogen Storage in an Activated Carbon Electrode

Authors: Sh. Heidari, A. J. Andrews, A. Oberoi

Abstract:

Electrochemical storage of hydrogen in activated carbon electrodes as part of a reversible fuel cell offers a potentially attractive option for storing surplus electrical energy from inherently variable solar and wind energy resources. Such a system – which we have called a proton flow battery – promises to have a roundtrip energy efficiency comparable to lithium ion batteries, while having higher gravimetric and volumetric energy densities. In this paper, a theoretical model is presented of the process of H+ ion (proton) conduction through an acid electrolyte into a highly porous activated carbon electrode where it is neutralised and absorbed on the inner surfaces of pores. A Butler-Volmer type equation relates the rate of adsorption to the potential difference between the activated carbon surface and the electrolyte. This model for the hydrogen storage electrode is then incorporated into a more general computer model based on MATLAB software of the entire electrochemical cell including the oxygen electrode. Hence a theoretical voltage-current curve is generated for given input parameters for a particular activated carbon electrode. It is shown that theoretical VI curves produced by the model can be fitted accurately to experimental data from an actual electrochemical cell with the same characteristics. By obtaining the best-fit values of input parameters, such as the exchange current density and charge transfer coefficient for the hydrogen adsorption reaction, an improved understanding of the adsorption reaction is obtained. This new model will assist in designing improved proton flow batteries for storing solar and wind energy.

Keywords: electrochemical hydrogen storage, proton flow battery, butler-volmer equation, activated carbon

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3056 Chemopreventive Efficacy of Andrographolide in Rat Colon Carcinogenesis Model Using Aberrant Crypt Foci (ACF) as Endpoint Marker

Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

Abstract:

Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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3055 Behavior of hFOB 1.19 Cells in Injectable Scaffold Composing of Pluronic F127 and Carboxymethyl Hexanoyl Chitosan

Authors: Lie-Sian Yap, Ming-Chien Yang

Abstract:

This study demonstrated a novel injectable hydrogel scaffold composing of Pluronic F127, carboxymethyl hexanoyl chitosan (CA) and glutaraldehyde (GA) for encapsulating human fetal osteoblastic cells (hFOB) 1.19. The hydrogel was prepared by mixing F127 and GA in CA solution at 4°C. The mechanical properties and cytotoxicity of this hydrogel were determined through rheological measurements and MTT assay, respectively. After encapsulation process, the hFOB 1.19 cells morphology was examined using fluorescent and confocal imaging. The results indicated that the Tgel of this system was around 30°C, where sol-gel transformation occurred within 90s and F127/CA/GA gel was able to remain intact in the medium for more than 1 month. In vitro cell culture assay revealed that F127/CA/GA hydrogels were non-cytotoxic. Encapsulated hFOB 1.19 cells not only showed the spherical shape and formed colonies, but also reduced their size. Moreover, the hFOB 1.19 cells showed that cells remain alive after the encapsulation process. Based on these results, these F127/CA/GA hydrogels can be used to encapsulate cells for tissue engineering applications.

Keywords: carboxymethyl hexanoyl chitosan, cell encapsulation, hFOB 1.19, Pluronic F127

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3054 GaAs Based Solar Cells: Growth, Fabrication, and Characterization

Authors: Hülya Kuru Mutlu, Mustafa Kulakcı, Uğur Serincan

Abstract:

The sun is one of the latest developments in renewable energy sources, which has a variety of application. Solar energy is the most preferred renewable energy sources because it can be used directly, it protects the environment and it is economic. In this work, we investigated that important parameter of GaAs-based solar cells with respect to the growth temperature. The samples were grown on (100) oriented p-GaAs substrates by solid source Veeco GEN20MC MBE system equipped with Ga, In, Al, Si, Be effusion cells and an Arsenic cracker cell. The structures of the grown samples are presented. After initial oxide desorption, Sample 1 and Sample 2 were grown at about 585°C and 535°C, respectively. From the grown structures, devices were fabricated by using the standard photolithography procedure. Current-voltage measurements were performed at room temperature (RT). It is observed that Sample 1 which was grown at 585°C has higher efficiency and fill factor compared to Sample 2. Hence, it is concluded that the growth temperature of 585°C is more suitable to grow GaAs-based solar cells considering our samples used in this study.

Keywords: molecular beam epitaxy, solar cell, current-voltage measurement, Sun

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3053 Intraspecific Response of the Ciliate Tetrahymena thermophila to Copper and Thermal Stress

Authors: Doufoungognon Carine Kone

Abstract:

Heavy metals present in large quantities in ecosystems can alter biological and cellular functions and disrupt trophic functions. However, their toxicity can change according to thermal conditions, as toxicity depends on their bioavailability and thermal optimum of organisms. Organisms can develop different tolerance strategies to maintain themselves in a stressful environment, but these strategies are often studied in a single-stressor context. This study evaluates the responses of the ciliate Tetrahymena thermophila to copper, high temperature, and their interaction. Six genotypes were exposed to a gradient of copper concentrations ranging from 0 to 350mg/L in synthetic media at three temperatures: 15°C, 23°C, and 31°C. Cell density, cell shape and size (and their variance), swimming speed and trajectory, and copper uptake rate were measured. Depending on the genotype, swimming speed, trajectory, and cell size were highly affected by stress gradients. One gets bigger, while two genotypes get smaller and the other remain unchanged. Some genotypes swam less rapidly, while others speed up as copper and temperature increased. Concerning copper uptake, the two genotypes accumulating the best and the worst, whatever the copper concentration or temperature, were also those that had the highest densities. Finally, very few temperature x copper interactions were observed on phenotypic parameters. The diversity of phenotypic responses revealed in this study reflects the existence of divergent strategies adopted by Tetrahymena thermophila to resist to copper and thermal stress, which suggests an important role of intraspecific variability in biodiversity response to environmental stress. One general and the surprising pattern was a global absence of interactive effects between copper and high temperature exposure on the observed phenotypic responses.

Keywords: ciliate, copper, intraspecific variability, phenotype, temperature, tolerance, multiple stressors

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3052 Cytotoxic Effects of Engineered Nanoparticles in Human Mesenchymal Stem Cells

Authors: Ali A. Alshatwi, Vaiyapuri S. Periasamy, Jegan Athinarayanan

Abstract:

Engineered nanoparticles’ usage rapidly increased in various applications in the last decade due to their unusual properties. However, there is an ever increasing concern to understand their toxicological effect in human health. Particularly, metal and metal oxide nanoparticles have been used in various sectors including biomedical, food and agriculture. But their impact on human health is yet to be fully understood. In this present investigation, we assessed the toxic effect of engineered nanoparticles (ENPs) including Ag, MgO and Co3O4 nanoparticles (NPs) on human mesenchymal stem cells (hMSC) adopting cell viability and cellular morphological changes as tools The results suggested that silver NPs are more toxic than MgO and Co3O4NPs. The ENPs induced cytotoxicity and nuclear morphological changes in hMSC depending on dose. The cell viability decreases with increase in concentration of ENPs. The cellular morphology studies revealed that ENPs damaged the cells. These preliminary findings have implications for the use of these nanoparticles in food industry with systematic regulations.

Keywords: cobalt oxide, human mesenchymal stem cells, MgO, silver

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3051 A Retrospective Study of Vaginal Stenosis Following Treatment of Cervical Cancers and the Effectiveness of Rehabilitation Interventions

Authors: Manjusha R. Vagal, Shyam K. Shrivastava, Umesh Mahantshetty, Sudeep Gupta, Supriya Chopra, Reena Engineer, Amita Maheshwari, Atul Buduk

Abstract:

Vaginal stenosis is a common side effect associated with pelvic radiotherapy in cervical cancer patients which contributes negatively to woman’s health and prevents adequate vaginal/cervical examination. Vaginal dilation with a dilator is routine practice and is internationally advocated as a prophylactic measure to preserve vaginal patency. This retrospective study was carried out with the aim to know the usefulness of vaginal dilation following pelvic radiation therapy in cervical cancer patients in India. Data from medical records of 183 cervical cancer patients, which met the study criteria, were collected related to the stage of the disease, treatment received, commencement period of dilation post radiation therapy, sexual status and side effects associated to dilation practice. Data related to vaginal dimensions as per the length of insertion of a small, medium and large dilator were collected on regular follow-ups until 36 months and/or more. Vaginal dimensions as measured with the length of medium dilator insertion were used for analysis of dilation therapy results using paired t-test. Patients who underwent vaginal dilation with dilator maintained vaginal patency, also the mean vaginal length significantly increased, from 8.02 cm ± 2.69 to 9.96 ± 2.89 cm with a p value <0.001. There was no significant difference found on vaginal patency with different intervals of initiation of dilation therapy. At the third year and more following dilation therapy, significant increase in vaginal length observed with a p value of 0.0001 in both sexually active and inactive patients. Compilation of vaginal dosage during brachytherapy was inadequate, and hence, the secondary objective of the study to determine the effect of radiotherapy on the outcome of rehabilitation intervention was not studied in detail. This retrospective study has found that dilation therapy with vaginal dilators post pelvic radiotherapy is effective in preventing vaginal stenosis and improving vaginal patency and cannot be substituted with vaginal intercourse. Sexual quality of life assessment in the Indian population needs much attention.

Keywords: dilator, sexually active, vaginal dilation, vaginal stenosis

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3050 Study of the Genotoxic Potential of Plant Growth Regulator Ethephon

Authors: Mahshid Hodjat, Maryam Baeeri, Mohammad Amin Rezvanfar, Mohammad Abdollahi

Abstract:

Ethephon is one of the most widely used plant growth regulator in agriculture that its application has been increased in recent years. The toxicity of organophosphate compounds is mostly attributed to their potent inhibition of acetylcholinesterase and their involvement in neurodegenerative disease. Although there are few reports on butyrylcholinesterase inhibitory role of ethephon, still there is no evidence on neurotoxicity and genotoxicity of this compound. The aim of the current study is to assess the potential genotoxic effect of ethephon using two genotoxic endpoints; γH2AX expression and comet assay on embryonic murine fibroblast. γH2AX serves as an early and sensitive biomarker for evaluating the genotoxic effects of chemicals. Oxidative stress biomarkers, including intracellular reactive oxygen species, lipid peroxidation and antioxidant capacity were also examined. The results showed a significant increase in cell proliferation 24h post-treatment with 10, 40,160µg/ml ethephon. The γH2AX expression and γH2AX foci count per cell were increased at low concentration of ethephon that was concomitant with increased DNA damage break at 40 and 160 µg/ml as illustrated by increased comet tail moment. A significant increase in lipid peroxidation and ROS formation were observed at 160 µg/ml and higher doses. The results showed that low-dose of ethephon promoted cell proliferation while induce DNA damage, raising the possibility of ethephon mutagenicity. Ethephon-induced genotoxic effect of low dose might not related to oxidative damage. However, ethephon was found to increase oxidative stress at higher doses, lead to cellular cytotoxicity. Taken together, all data indicated that ethylene, deserves more attention as a plant regulator with potential genotoxicity for which appropriate control is needed to reduce its usage.

Keywords: ethephon, DNA damage, γH2AX, oxidative stress

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3049 Germline Mutations of Mitogen-Activated Protein Kinases Pathway Signaling Pathway Genes in Children

Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

Abstract:

Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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3048 Interferon-Induced Transmembrane Protein-3 rs12252-CC Associated with the Progress of Hepatocellular Carcinoma by Up-Regulating the Expression of Interferon-Induced Transmembrane Protein 3

Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

Abstract:

Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

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3047 Performance of a Lytic Bacteriophage Cocktail against Pseudomonas aeruginosa in Conditions That Simulate the Cystic Fibrosis Lung Environment

Authors: Isaac Martin, Abigail Lark, Sandra Morales, Eric W. Alton, Jane C. Davies

Abstract:

Objectives: The cystic fibrosis (CF) lung is a unique microbiological niche, wherein harmful bacteria persist for many years despite antibiotic therapy. Pseudomonas aeruginosa (Pa), the major culprit leading to lung decline and increased mortality, thrives in the lungs of patients with CF due to several factors that have been linked with poor antibiotic performance. Our group is investigating alternative therapies including bacteriophage cocktails with which we have previously demonstrated efficacy against planktonic organisms. In this study, we explored the effects of a 4-phage cocktail on Pa grown in two different conditions, intended to mirror the CF lung: a) alongside standard antibiotic treatment in pre-formed biofilms (structures formed by Pa-secreted exopolysaccharides which provide both physical and cell division barriers to antimicrobials and host defenses and b) in an acidic environment postulated to be present in the CF airway due both to the primary defect in bicarbonate secretion and secondary effects of inflammation. Methods: 16 Pa strains from CF patients at the Royal Brompton Hospital were selected based on sensitivity to a) ceftazidime/ tobramycin and b) the phage cocktail in a conventional plaque assay. To assess efficacy of phage in biofilms, 96 well plates with Pa (5x10⁷ CFU/ ml) were incubated in static conditions, allowing adherent bacterial colonies to form for 24 hr. Ceftazidime and tobramycin (both at 2 × MIC) were added, +/- bacteriophage (4x10⁸ PFU/mL) for a further 24 hr. Cell viability and biomass were estimated using fluorescent resazurin and crystal violet assays, respectively. To evaluate the effect of pH, strains were grown planktonically in shaking 96 well plates at pH 6.0, 6.6, 7.0 and 7.5 with tobramycin or phage, at varying concentrations. Cell viability was quantified by fluorescent resazurin assay. Results: For the biofilm assay, treatment groups were compared with untreated controls and expressed as percent reduction in cell viability and biomass. Addition of the 4-phage cocktail resulted in a 1.3-fold reduction in cell viability and 1.7-fold reduction in biomass (p < 0.001) when compared to standard antibiotic treatment alone. Notably, there was a 50 ± 15% reduction in cell viability and 60 ± 12% reduction in biomass (95% CI) for the 4 biofilms demonstrating the most resistance to antibiotic treatment. 83% of strains tested (n=6) showed decreased bacterial killing by tobramycin at acidic pHs (p < 0.01). However, 25% of strains (n=12) showed improved phage killing at acidic pHs (p < 0.05), with none showing the pattern of reduced efficacy at acidic pH demonstrated by tobramycin. Conclusion: The 4-phage anti-Pa cocktail tested against Pa performs well in pre-formed biofilms and in acidic environments; two conditions intended to mimic the CF lung. To our knowledge, these are the first data looking at the effects of subtle pH changes on phage-mediated bacterial killing in the context of Pa infection. These findings contribute to a growing body of evidence supporting the use of nebulised lytic bacteriophage as a treatment in the context of lung infection.

Keywords: biofilm, cystic fibrosis, pH, Pseudomonas aeruginosa, lytic bacteriophage

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3046 A 5G Architecture Based to Dynamic Vehicular Clustering Enhancing VoD Services Over Vehicular Ad hoc Networks

Authors: Lamaa Sellami, Bechir Alaya

Abstract:

Nowadays, video-on-demand (VoD) applications are becoming one of the tendencies driving vehicular network users. In this paper, considering the unpredictable vehicle density, the unexpected acceleration or deceleration of the different cars included in the vehicular traffic load, and the limited radio range of the employed communication scheme, we introduce the “Dynamic Vehicular Clustering” (DVC) algorithm as a new scheme for video streaming systems over VANET. The proposed algorithm takes advantage of the concept of small cells and the introduction of wireless backhauls, inspired by the different features and the performance of the Long Term Evolution (LTE)- Advanced network. The proposed clustering algorithm considers multiple characteristics such as the vehicle’s position and acceleration to reduce latency and packet loss. Therefore, each cluster is counted as a small cell containing vehicular nodes and an access point that is elected regarding some particular specifications.

Keywords: video-on-demand, vehicular ad-hoc network, mobility, vehicular traffic load, small cell, wireless backhaul, LTE-advanced, latency, packet loss

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3045 Oxidative Antioxidative Status and DNA Damage Profile Induced by Chemotherapy in Algerian Children with Lymphoma

Authors: Assia Galleze, Abdurrahim Kocyigit, Nacira Cherif, Nidel Benhalilou, Nabila Attal, Chafia Touil Boukkoffa, Rachida Raache

Abstract:

Introduction and aims: Chemotherapeutic agents used to inhibit cell division and reduce tumor growth, increase reactive oxygen species levels, which contributes to their genotoxicity [1]. The comet assay is an inexpensive and rapid method to detect the damage at cellular levels and has been used in various cancer populations undergoing chemotherapy [2,3]. The present study aim to assess the oxidative stress and the genotoxicity induced by chemotherapy by the determination of plasma malondialdehyde (MDA) level, protein carbonyl (PC) content, superoxide dismutase (SOD) activity and lymphocyte DNA damage in Algerian children with lymphoma. Materials and Methods: For our study, we selected thirty children with lymphoma treated in university hospital of Beni Messous, Algeria, and fifty unrelated subjects as controls, after obtaining the informed consent in accordance with the Declaration of Helsinki (1964). Plasma levels of MDA, PC and SOD activity were spectrophotometrically measured, while DNA damage was assessed by alkaline comet assay in peripheral blood leukocytes. Results and Discussion: Plasma MDA, PC levels and lymphocyte DNA damage, were found to be significantly higher in lymphoma patients than in controls (p < 0.001). Whereas, SOD activity in lymphoma patients was significantly lower than in healthy controls (p < 0.001). There were significant positive correlations between DNA damage, MDA and PC in patients (r = 0.96, p < 0.001, r = 0.97, p < 0.001, respectively), and negative correlation with SOD (r = 0.87, p < 0.01). Conclusion and Perspective: Our results indicated that, leukocytes DNA damage and oxidative stress were significantly higher in lymphoma patients, suggesting that the direct effect of chemotherapy and the alteration of the redox balance may influence oxidative/antioxidative status.

Keywords: chemotherapy, comet assay, DNA damage, lymphoma

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3044 Numerical Optimization of Cooling System Parameters for Multilayer Lithium Ion Cell and Battery Packs

Authors: Mohammad Alipour, Ekin Esen, Riza Kizilel

Abstract:

Lithium-ion batteries are a commonly used type of rechargeable batteries because of their high specific energy and specific power. With the growing popularity of electric vehicles and hybrid electric vehicles, increasing attentions have been paid to rechargeable Lithium-ion batteries. However, safety problems, high cost and poor performance in low ambient temperatures and high current rates, are big obstacles for commercial utilization of these batteries. By proper thermal management, most of the mentioned limitations could be eliminated. Temperature profile of the Li-ion cells has a significant role in the performance, safety, and cycle life of the battery. That is why little temperature gradient can lead to great loss in the performances of the battery packs. In recent years, numerous researchers are working on new techniques to imply a better thermal management on Li-ion batteries. Keeping the battery cells within an optimum range is the main objective of battery thermal management. Commercial Li-ion cells are composed of several electrochemical layers each consisting negative-current collector, negative electrode, separator, positive electrode, and positive current collector. However, many researchers have adopted a single-layer cell to save in computing time. Their hypothesis is that thermal conductivity of the layer elements is so high and heat transfer rate is so fast. Therefore, instead of several thin layers, they model the cell as one thick layer unit. In previous work, we showed that single-layer model is insufficient to simulate the thermal behavior and temperature nonuniformity of the high-capacity Li-ion cells. We also studied the effects of the number of layers on thermal behavior of the Li-ion batteries. In this work, first thermal and electrochemical behavior of the LiFePO₄ battery is modeled with 3D multilayer cell. The model is validated with the experimental measurements at different current rates and ambient temperatures. Real time heat generation rate is also studied at different discharge rates. Results showed non-uniform temperature distribution along the cell which requires thermal management system. Therefore, aluminum plates with mini-channel system were designed to control the temperature uniformity. Design parameters such as channel number and widths, inlet flow rate, and cooling fluids are optimized. As cooling fluids, water and air are compared. Pressure drop and velocity profiles inside the channels are illustrated. Both surface and internal temperature profiles of single cell and battery packs are investigated with and without cooling systems. Our results show that using optimized Mini-channel cooling plates effectively controls the temperature rise and uniformity of the single cells and battery packs. With increasing the inlet flow rate, cooling efficiency could be reached up to 60%.

Keywords: lithium ion battery, 3D multilayer model, mini-channel cooling plates, thermal management

Procedia PDF Downloads 152
3043 Lymphomas as Estrogen-Regulated Cancers

Authors: M. S. Hasni, J. Guan, K. Yakimchuk, M. Berglund, B. Sander, G. Enblad, R. M. Amini, S. Okret

Abstract:

Lymphomas are generally not considered as endocrine-related cancers. However, most lymphoid malignancies show gender differences in incidence and show prognosis with males being more affected. Furthermore, some epidemiological data indicate a protective role of estrogens against Non-Hodgkin lymphomas. Recent studies have demonstrated estrogen receptor β (ERβ) to be the major ER expressed in normal and malignant cells of lymphoid origin. We have analyzed the effects of estradiol and selective ERα and ERβ agonists on lymphoma growth in culture and in vivo. Treating lymphoma cells with estradiol or ERα selective agonist had minor or no effect on cell growth while selective ERβ agonist treatment showed an antiproliferative effect. When grafting mice with murine T lymphoma cells, male mice developed larger tumors compared to female mice, a difference that was abolished following ovariectomy, demonstrating estrogen-dependent growth in vivo. When subcutaneously grafting lymphoma cells to mice, so far growth of all tested human B lymphoma tumors (Raji and Ramos Burkitt lymphoma, SU.DHL4 (GC) and U2932 (ABC) DLBCL, Granta-519, Maver1 and Z138 MCL cells), were reduced following treatment with ERβ selective agonist (ref. 2 and unpublished). Moreover, the number and size of liver foci of disseminating Raji cells was reduced. We have identified target genes and mechanism that could explain the above effects of ERβ agonists. This included effects on angio and lymphangiogenesis. Now we have further analyzed effects of ERβ agonists on Ibrutinib-sensitive and -insensitive MCL cells in xenograft experiments as well as ERβ expression in primary lymphoma material (DLBCL). Preliminary statistical analysis has been done correlating ERβ expression to other biomarkers and clinical data.

Keywords: lymphomas, estrogen receptors, cancer, liver foci

Procedia PDF Downloads 396
3042 Development of Chitosan/Dextran Gelatin Methacrylate Core/Shell 3D Scaffolds and Protein/Polycaprolactone Melt Electrowriting Meshes for Tissue Regeneration Applications

Authors: J. D. Cabral, E. Murray, P. Turner, E. Hewitt, A. Ali, M. McConnell

Abstract:

Worldwide demand for organ replacement and tissue regeneration is progressively increasing. Three-dimensional (3D) bioprinting, where a physical construct is produced using computer-aided design, is a promising tool to advance the tissue engineering and regenerative medicine fields. In this paper we describe two different approaches to developing 3D bioprinted constructs for use in tissue regeneration. Bioink development is critical in achieving the 3D biofabrication of functional, regenerative tissues. Hydrogels, cross-linked macromolecules that absorb large amounts of water, have received widespread interest as bioinks due to their relevant soft tissue mechanics, biocompatibility, and tunability. In turn, not only is bioink optimisation crucial, but the creation of vascularized tissues remains a key challenge for the successful fabrication of thicker, more clinically relevant bioengineered tissues. Among the various methodologies, cell-laden hydrogels are regarded as a favorable approach; and when combined with novel core/shell 3D bioprinting technology, an innovative strategy towards creating new vessel-like structures. In this work, we investigate this cell-based approach by using human umbilical endothelial cells (HUVECs) entrapped in a viscoelastic chitosan/dextran (CD)-based core hydrogel, printed simulataneously along with a gelatin methacrylate (GelMA) shell. We have expanded beyond our previously reported FDA approved, commercialised, post-surgical CD hydrogel, Chitogel®, by functionalizing it with cell adhesion and proteolytic peptides in order to promote bone marrow-derived mesenchymal stem cell (immortalized BMSC cell line, hTERT) and HUVECs growth. The biocompatibility and biodegradability of these cell lines in a 3D bioprinted construct is demonstrated. Our studies show that particular peptide combinations crosslinked within the CD hydrogel was found to increase in vitro growth of BMSCs and HUVECs by more than two-fold. These gels were then used as a core bioink combined with the more mechanically robust, UV irradiated GelMA shell bioink, to create 3D regenerative, vessel-like scaffolds with high print fidelity. As well, microporous MEW scaffolds made from milk proteins blended with PCL were found to show promising bioactivity, exhibiting a significant increase in keratinocyte (HaCaTs) and fibroblast (normal human dermal fibroblasts, NhDFs) cell migration and proliferation when compared to PCL only scaffolds. In conclusion, our studies indicate that a peptide functionalized CD hydrogel bioink reinforced with a GelMA shell is biocompatible, biodegradable, and an appropriate cell delivery vehicle in the creation of regenerative 3D constructs. In addition, a novel 3D printing technique, melt electrowriting (MEW), which allows fabrication of micrometer fibre meshes, was used to 3D print polycaprolactone (PCL) and bioactive milk protein, lactorferrin (LF) and whey protein (WP), blended scaffolds for potential skin regeneration applications. MEW milk protein/PCL scaffolds exhibited high porosity characteristics, low overall biodegradation, and rapid protein release. Human fibroblasts and keratinocyte cells were seeded on to the scaffolds. Scaffolds containing high concentrations of LF and combined proteins (LF+WP) showed improved cell viability over time as compared to PCL only scaffolds. This research highlights two scaffolds made using two different 3D printing techniques using a combination of both natural and synthetic biomaterial components in order to create regenerative constructs as potential chronic wound treatments.

Keywords: biomaterials, hydrogels, regenerative medicine, 3D bioprinting

Procedia PDF Downloads 252
3041 A Study of The Factors Predicting Radiation Exposure to Contacts of Saudi Patients Treated With Low-Dose Radioactive Iodine (I-131)

Authors: Khalid A. Salman, Shereen Wagih, Tariq Munshi, Musaed Almalki, Safwan Zatari, Zahid Khan

Abstract:

Aim: To measure exposure levels to family members and caregivers of Saudi patients treated with low dose I131 therapy, and household radiation exposure rate to predict different factors that can affect radiation exposure. Patients and methods: All adult self dependent patients with hyperthyroidism or cancer thyroid referred for low dose radioactive I131 therapy on outpatient basis are included. Radiation protection procedures are given to the participant and family members in details. TLD’s were dispensed to each participant in sufficient quantity for his/her family members living in the household. TLD’s are collected at fifth days post-dispense from patients who agreed to have a home visit during which the household is inspected and level of radiation contamination of surfaces was measured. Results: Thirty-two patients were enrolled in the current study, with a mean age of 43.1± 17.1 years Out of them 25 patients (78%) are females. I131 therapy was given in twenty patients (63%) for cancer thyroid of and for toxic goiter in the remaining twelve patients (37%), with an overall mean I131 dose of 24.1 ± 7.5mCi that is relatively higher in the former. The overall number of household family members and helpers of patients are 139, out of them77 are females (55.4%) & 62 are males (44.6%) with a mean age of 29.8± 17.6. The mean period of contact with the patient is 7.6 ±5.6hours. The cumulative radiation exposure shows that radiation exposure to all family members is below the exposure constraint (1mSv), with a range of 109 to 503uSv, and a mean value of 220.9±91 uSv. Numerical data shows a little higher exposure rate for family members of those who receive higher dose of I131 (patients with thyroid cancer) and household members who spent longer time with the patient, yet, the difference is statistically insignificant (P>0.05). Besides, no significant correlation was found between the degree of cumulative exposure of the family members to their gender, age, socioeconomic standard, educational level and residential factors. In the 21 home visits all data from bedrooms, reception areas and kitchens are below hazardous limits (0.5uSv/h) apart from bathrooms that give a slightly higher reading of 0.57±0.39 uSv/h in those with cancer thyroid who receive a higher radiation dose. A statistically significant difference was found between radiation exposure rate in bathrooms used by the patient versus those used by family members only, with a mean value of exposure rate of 0.701±0.21 uSv/h and 0.17±0.82 uSv/h respectively, with a p-value of 0.018 (<0.05). Conclusion: Family members of patients treated with low dose I131 on outpatient basis have a good compliance to radiation protection instruction if given properly with a cumulative radiation exposure rate evidently beyond the radiation exposure constraints of 1 mSv. Given I131 dose, hours spent with the patient, age, gender, socioeconomic standard, educational level and residential factors have no significant correlation with the cumulative radiation exposure. The patient bathroom exhibits more radiation exposure rate, needing more strict instructions for patient bathroom use and health hygiene.

Keywords: family members, radiation exposure, radioactive iodine therapy, radiation safety

Procedia PDF Downloads 261
3040 Raman Spectroscopic of Cardioprotective Mechanism During the Metabolic Inhibition of Heart Cells

Authors: A. Almohammedi, A. J. Hudson, N. M. Storey

Abstract:

Following ischaemia/reperfusion injury, as in a myocardial infraction, cardiac myocytes undergo oxidative stress which leads to several potential outcomes including; necrotic or apoptotic cell death or dysregulated calcium homeostasis or disruption of the electron transport chain. Several studies have shown that nitric oxide donors protect cardiomyocytes against ischemia and reperfusion. However until present, the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes is not fully understood and has not been investigated before using Raman spectroscopy. For these reasons, the aim of this study was to develop a novel technique, pre-resonance Raman spectroscopy, to investigate the mechanism of cardioprotective effect of nitric oxide donor in isolated ventricular cardiomyocytes exposed to metabolic inhibition and re-energisation. The results demonstrated the first time that Raman microspectroscopy technique has the capability to monitor the metabolic inhibition of cardiomyocytes and to monitor the effectiveness of cardioprotection by nitric oxide donor prior to metabolic inhibition of cardiomyocytes. Metabolic inhibition and reenergisation were used in this study to mimic the low and high oxygen levels experienced by cells during ischaemic and reperfusion treatments. A laser wavelength of 488 nm used in this study has been found to provide the most sensitive means of observe the cellular mechanisms of myoglobin during nitric oxide donor preconditioning, metabolic inhibition and re-energisation and did not cause any damage to the cells. The data also highlight the considerably different cellular responses to metabolic inhibition to ischaemia. Moreover, the data has been shown the relationship between the release of myoglobin and chemical ischemia where that the release of myoglobin from the cell only occurred if a cell did not recover contractility.

Keywords: ex vivo biospectroscopy, Raman spectroscopy, biophotonics, cardiomyocytes, ischaemia / reperfusion injury, cardioprotection, nitric oxide donor

Procedia PDF Downloads 336
3039 Noninvasive Disease Diagnosis through Breath Analysis Using DNA-functionalized SWNT Sensor Array

Authors: W. J. Zhang, Y. Q. Du, M. L. Wang

Abstract:

Noninvasive diagnostics of diseases via breath analysis has attracted considerable scientific and clinical interest for many years and become more and more promising with the rapid advancement in nanotechnology and biotechnology. The volatile organic compounds (VOCs) in exhaled breath, which are mainly blood borne, particularly provide highly valuable information about individuals’ physiological and pathophysiological conditions. Additionally, breath analysis is noninvasive, real-time, painless and agreeable to patients. We have developed a wireless sensor array based on single-stranded DNA (ssDNA)-decorated single-walled carbon nanotubes (SWNT) for the detection of a number of physiological indicators in breath. Eight DNA sequences were used to functionalize SWNT sensors to detect trace amount of methanol, benzene, dimethyl sulfide, hydrogen sulfide, acetone and ethanol, which are indicators of heavy smoking, excessive drinking, and diseases such as lung cancer, breast cancer, cirrhosis and diabetes. Our tests indicated that DNA functionalized SWNT sensors exhibit great selectivity, sensitivity, reproducibility, and repeatability. Furthermore, different molecules can be distinguished through pattern recognition enabled by this sensor array. Thus, the DNA-SWNT sensor array has great potential to be applied in chemical or bimolecular detection for the noninvasive diagnostics of diseases and health monitoring.

Keywords: breath analysis, diagnosis, DNA-SWNT sensor array, noninvasive

Procedia PDF Downloads 333
3038 The Effects of Androgen Receptor Mutation on Cryptorchid Testes in 46, XY Female

Authors: Ihtisham Bukhari

Abstract:

In the current study, we enrolled a 46, XY phenotypically female patient bearing testes in her inguinal canal. DNA sequencing of the AR gene detected a missense mutation C.1715A > G (p. Y572C) in exon 2 which is already known to cause Complete androgen insensitivity syndrome (CAIS). We further studied the effects of this mutation on the testicular histopathology of the patient. No spermatocytes were seen in the surface spreading of testicular tissues while H&E staining showed that seminiferous tubules predominantly have only Sertoli cells. To confirm this meiotic failure is likely due to the current AR mutation we performed mRNA expression of genes associated with AR pathway, expression and location of the associated proteins in testicular tissues. Western blot and real-time PCR data showed that the patient had high levels of expression of AMH, SOX9, and INNB in testis. Tubules were stained with SOX9 and AMH which revealed Sertoli cell maturation arrest. Therefore, we suggest that AR mutation enhances AMH expression which ultimately leads to failure in the maturation of Sertoli cells and failure in spermatogenesis.

Keywords: androgen receptor, spermatogenesis, infertility, Sertoli cell only syndrome

Procedia PDF Downloads 127
3037 Electrochemical Study of Prepared Cubic Fluorite Structured Titanium Doped Lanthanum Gallium Cerate Electrolyte for Low Temperature Solid Oxide Fuel Cell

Authors: Rida Batool, Faizah Altaf, Saba Nadeem, Afifa Aslam, Faisal Alamgir, Ghazanfar Abbas

Abstract:

Today, the need of the hour is to find out alternative renewable energy resources in order to reduce the burden on fossil fuels and prevent alarming environmental degradation. Solid oxide fuel cell (SOFC) is considered a good alternative energy conversion device because it is environmentally benign and supplies energy on demand. The only drawback associated with SOFC is its high operating temperature. In order to reduce operating temperature, different types of composite material are prepared. In this work, titanium doped lanthanum gallium cerate (LGCT) composite is prepared through the co-precipitation method as electrolyte and examined for low temperature SOFCs (LTSOFCs). The structural properties are analyzed by X-Ray Diffractometry (XRD) and Fourier Transform Infrared (FTIR) Spectrometry. The surface properties are investigated by Scanning Electron Microscopy (SEM). The electrolyte LGCT has the formula LGCTO₃ because it showed two phases La.GaO and Ti.CeO₂. The average particle size is found to be (32 ± 0.9311) nm. The ionic conductivity is achieved to be 0.073S/cm at 650°C. Arrhenius plots are drawn to calculate activation energy and found 2.96 eV. The maximum power density and current density are achieved at 68.25mW/cm² and 357mA/cm², respectively, at 650°C with hydrogen. The prepared material shows excellent ionic conductivity at comparatively low temperature, that makes it a potentially good candidate for LTSOFCs.

Keywords: solid oxide fuel cell, LGCTO₃, cerium composite oxide, ionic conductivity, low temperature electrolyte

Procedia PDF Downloads 96
3036 Fluid Structure Interaction of Flow and Heat Transfer around a Microcantilever

Authors: Khalil Khanafer

Abstract:

This study emphasizes on analyzing the effect of flow conditions and the geometric variation of the microcantilever’s bluff body on the microcantilever detection capabilities within a fluidic device using a finite element fluid-structure interaction model. Such parameters include inlet velocity, flow direction, and height of the microcantilever’s supporting system within the fluidic cell. The transport equations are solved using a finite element formulation based on the Galerkin method of weighted residuals. For a flexible microcantilever, a fully coupled fluid-structure interaction (FSI) analysis is utilized and the fluid domain is described by an Arbitrary-Lagrangian–Eulerian (ALE) formulation that is fully coupled to the structure domain. The results of this study showed a profound effect on the magnitude and direction of the inlet velocity and the height of the bluff body on the deflection of the microcantilever. The vibration characteristics were also investigated in this study. This work paves the road for researchers to design efficient microcantilevers that display least errors in the measurements.

Keywords: fluidic cell, FSI, microcantilever, flow direction

Procedia PDF Downloads 363
3035 Projected Impact of Population Aging on Noncommunicable Disease Burden and Costs in the Kingdom of Saudi Arabia, 2020–2030

Authors: David C. Boettiger, Tracy Kuo Lin, Maram Almansour, Mariam M. Hamza, Reem Alsukait, Christopher H. Herbst, Nada Altheyab, Ayman Afghani, Faisal Kattan

Abstract:

Background The number of people aged greater than 65 years per 100 people aged 20–64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. Methods Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. Results The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8 billion in 2020 to USD 32.4 billion in 2030 (an increase of USD 12.6 billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3 billion), diabetes (USD 2.4 billion), and dementia (USD 1.9 billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2 billion - USD 35.7 billion. Conclusions Managing the growing NCD burden in KSA’s aging population will require substantial healthcare spending increases over the coming years.

Keywords: aging, non communicable disease, costs, Saudi Arabia

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3034 Mining the Proteome of Fusobacterium nucleatum for Potential Therapeutics Discovery

Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

Abstract:

The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

Procedia PDF Downloads 369
3033 Biodegradable Cross-Linked Composite Hydrogels Enriched with Small Molecule for Osteochondral Regeneration

Authors: Elena I. Oprita, Oana Craciunescu, Rodica Tatia, Teodora Ciucan, Reka Barabas, Orsolya Raduly, Anca Oancea

Abstract:

Healing of osteochondral defects requires repair of the damaged articular cartilage, the underlying subchondral bone and the interface between these tissues (the functional calcified layer). For this purpose, developing a single monophasic scaffold that can regenerate two specific lineages (cartilage and bone) becomes a challenge. The aim of this work was to develop variants of biodegradable cross-linked composite hydrogel based on natural polypeptides (gelatin), polysaccharides components (chondroitin-4-sulphate and hyaluronic acid), in a ratio of 2:0.08:0.02 (w/w/w) and mixed with Si-hydroxyapatite (Si-Hap), in two ratios of 1:1 and 2:1 (w/w). Si-Hap was synthesized and characterized as a better alternative to conventional Hap. Subsequently, both composite hydrogel variants were cross-linked with (N, N-(3-dimethylaminopropyl)-N-ethyl carbodiimide (EDC) and enriched with a small bioactive molecule (icariin). The small molecule icariin (Ica) (C33H40O15) is the main active constituent (flavonoid) of Herba epimedium used in traditional Chinese medicine to cure bone- and cartilage-related disorders. Ica enhances osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), facilitates matrix calcification and increases the specific extracellular matrix (ECM) components synthesis by chondrocytes. Afterward, the composite hydrogels were characterized for their physicochemical properties in terms of the enzymatic biodegradation in the presence of type I collagenase and trypsin, the swelling capacity and the degree of crosslinking (TNBS assay). The cumulative release of Ica and real-time concentration were quantified at predetermined periods of time, according to the standard curve of standard Ica, after hydrogels incubation in saline buffer at physiological parameters. The obtained cross-linked composite hydrogels enriched with small-molecule Ica were also characterized for morphology by scanning electron microscopy (SEM). Their cytocompatibility was evaluated according to EN ISO 10993-5:2009 standard for medical device testing. Thus, analyses regarding cell viability (Live/Dead assay), cell proliferation (Neutral Red assay) and cell adhesion to composite hydrogels (SEM) were performed using NCTC clone L929 cell line. The final results showed that both cross-linked composite hydrogel variants enriched with Ica presented optimal physicochemical, structural and biological properties to be used as a natural scaffold able to repair osteochondral defects. The data did not reveal any toxicity of composite hydrogels in NCTC stabilized cell lines within the tested range of concentrations. Moreover, cells were capable of spreading and proliferating on both composite hydrogel surfaces. In conclusion, the designed biodegradable cross-linked composites enriched with Si and Ica are recommended for further testing as natural temporary scaffolds, which can allow cell migration and synthesis of new extracellular matrix within osteochondral defects.

Keywords: composites, gelatin, osteochondral defect, small molecule

Procedia PDF Downloads 159
3032 Optimal Sputtering Conditions for Nickel-Cermet Anodes in Intermediate Temperature Solid Oxide Fuel Cells

Authors: Waqas Hassan Tanveer, Yoon Ho Lee, Taehyun Park, Wonjong Yu, Yaegeun Lee, Yusung Kim, Suk Won Cha

Abstract:

Nickel-Gadolinium Doped Ceria (Ni-GDC) cermet anodic thin films were prepared on Scandia Stabilized Zirconia (ScSZ) electrolyte supports by radio frequency (RF) sputtering, with a range of different sputtering powers (50 – 200W) and background Ar gas pressures (30 – 90mTorr). The effects of varying sputtering power and pressure on the properties of Ni-GDC films were studied using Focused Ion Beam (FIB), X-ray Photoelectron Spectroscopy (XPS), X-ray Diffraction (XRD), Energy Dispersive X-ray (EDX), and Atomic Force Microscopy (AFM) techniques. The Ni content was found to be always higher than the Ce content, at all sputtering conditions. This increased Ni content was attributed to significantly higher energy transfer efficiency of Ni ions as compared to Ce ions with Ar background sputtering gas. The solid oxide fuel cell configuration was completed by using lanthanum strontium manganite (LSM/YSZ) cathodes on the other side of ScSZ supports. Performance comparison of cells was done by Voltage-Current-Power (VIP) curves, while the resistances of various cell components were observed by nyquist plots. Initial results showed that anode films made by higher powered RF sputtering performed better than lower powered ones for a specific Ar pressure. Interestingly, however, anodes made at highest power and pressure, were not the ones that showed the maximum power output at an intermediate solid oxide fuel cell temperature of 800°C. Finally, an optimal sputtering condition was reported for high performance Ni-GDC anodes.

Keywords: intermediate temperature solid oxide fuel cells, nickel-cermet anodic thin films, nyquist plots, radio frequency sputtering

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3031 Investigation of Heavy Metals and Nitrate Level in Drinking Water and the Side Effects on Public Health in the Capital City of Iran

Authors: Iman Nazari, Behrouz Shaabani, Ali Ramouz

Abstract:

Regarding to the dramatic rise of cancer prevalence of cancers in Iran and also base on the investigations around environmental factors which causes cancer, The air and water pollution is in high level in Iran’s capital city this issue motivated us to start an investigation on concentration of heavy metals and nitrate in Tehran’s Tap water, additionally we investigated the effects of this contaminations on public health, it is clear that heavy metals and also nitrate are causes cancers directly and indirectly, we divided the city to four districts: (1) North, (2) East, (3) West, (4) South and totally collected over 30 samples from noted districts, we obvious difference in concentrations, after a study we founded the reasons of this difference, the old distribution system, non-standard sewage disposal system, travel up from contaminated rains, releasing industrial wastes waters without any pretreatment, the most important one is the old distribution system, Tehran is an old city hence distribution system is old too we know that the old water pipes were built from alloys which containing several of this harmful heavy metals, releasing of this heavy metals from pipes to the tap water is one of the most Important reasons, as the result we presented the concentrations by districts and the alternatives to decreasing the level of this contaminations.

Keywords: water quality, heavy metals, drinking water, environmental toxinology

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3030 Computer-Aided Classification of Liver Lesions Using Contrasting Features Difference

Authors: Hussein Alahmer, Amr Ahmed

Abstract:

Liver cancer is one of the common diseases that cause the death. Early detection is important to diagnose and reduce the incidence of death. Improvements in medical imaging and image processing techniques have significantly enhanced interpretation of medical images. Computer-Aided Diagnosis (CAD) systems based on these techniques play a vital role in the early detection of liver disease and hence reduce liver cancer death rate.  This paper presents an automated CAD system consists of three stages; firstly, automatic liver segmentation and lesion’s detection. Secondly, extracting features. Finally, classifying liver lesions into benign and malignant by using the novel contrasting feature-difference approach. Several types of intensity, texture features are extracted from both; the lesion area and its surrounding normal liver tissue. The difference between the features of both areas is then used as the new lesion descriptors. Machine learning classifiers are then trained on the new descriptors to automatically classify liver lesions into benign or malignant. The experimental results show promising improvements. Moreover, the proposed approach can overcome the problems of varying ranges of intensity and textures between patients, demographics, and imaging devices and settings.

Keywords: CAD system, difference of feature, fuzzy c means, lesion detection, liver segmentation

Procedia PDF Downloads 305